Transcriptional regulation in eukaryotes relies on factors that interact with specific sequences in gene promoters. This is a highly regulated and finely tuned process, which is critical to cell growth, differentiation and development and response to environmental changes. It is largely governed by negative and positive protein-protein interactions between regulatory factors, yet they are poorly understood. Understanding these interactions at the atomic level is key to understanding the mechanism of how transcriptional regulation works. The yeast GAL system, which serves as a paradigm for transcriptional regulation, provides a unique opportunity to examine these interactions at an atomic level, especially in light of the wealth of genetic information available. The objective of this proposal is to study the interactions and molecular characteristics of the factors involved in a transcriptional switch, and to shed light on the characteristics of activation domains, which remain largely enigmatic. Relevance: Transcriptional regulation in eukaryotes is a highly regulated and finely tuned process, which is critical to cell growth, differentiation and development and response to environmental changes. Our objective is to understand how this important type of regulation works on a very detailed atomic level.